CN101461843B - Medicament composition for ischemic disease and application thereof in medicinal preparation - Google Patents
Medicament composition for ischemic disease and application thereof in medicinal preparation Download PDFInfo
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- CN101461843B CN101461843B CN2009100736442A CN200910073644A CN101461843B CN 101461843 B CN101461843 B CN 101461843B CN 2009100736442 A CN2009100736442 A CN 2009100736442A CN 200910073644 A CN200910073644 A CN 200910073644A CN 101461843 B CN101461843 B CN 101461843B
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Abstract
The invention discloses a medicine composition for ischemic diseases, which comprises the following raw materials by weight portion: 5 to 15 portions of radix astragali, 2 to 8 portions of Salvia miltiorrhiza, 1 to 5 portions of ligusticum wallichii, 1 to 5 portions of safflower and 1 to 3 portions of earthworms. The invention simultaneously discloses application of the medicine composition in preparing pharmaceutical preparation for treating ischemic cerebrovascular disorder, application of the medicine composition in pharmaceutical preparation for treating ischemic cardiomyopathy, and application of the medicine composition in pharmaceutical preparation for treating ischemic enteropathy. The medicine composition can be used for preventing and treating ischemic diseases such as ischemic cerebrovascular disorder, ischemic cardiomyopathy and ischemic enteropathy, and can also be used for treating coronary heart disease, arteriosclerosis and mesenteric vein embolism. The medicine composition has strong pertinence and obvious medicine effect, and provides more application selections for clinical medication.
Description
Technical field
The present invention relates to pharmaceutical product and uses thereof, specifically a kind of pharmaceutical composition that is used for ischemic diseases and in the application of pharmaceutical preparation.
Background technology
Ischemic diseases is meant owing to arteriospasm, narrow, chronic occlusion make the organ of getting involved be in low blood flow state, causes atrophy, dysfunction even the necrosis of organ.Typical ischemic diseases includes cerebral infarction, ischemic cardiomyopathy, ischemic enteropathy etc.
Cerebral infarction is meant that the local feeding artery blood perfusion of the cerebral tissue of unexpected generation reduces or blood flow interrupts fully, stops blood supply, oxygen supply, supplies sugar etc., causes the cerebral tissue hypoxic-ischemic, a series of acute clinical symptoms occurs.If fail in time to recover blood supply, neurocyte, glial cell and blood vessel will be downright bad, form cerebral infarction.The main cause of cerebral infarction is: 1. thromboembolism due to the atherosclerosis; 2. cerebral embolism due to the embolus in heart source.According to the Pathophysiology evolution process, clinically cerebral infarction is divided into super early stage (in 6 hours of morbidity); (in the 6-72 of morbidity hour) in early days; The acute later stage (in 72 hours-1 weeks of morbidity); Convalescent period (after the week of morbidity).Cerebral infarction super early stage, disease time is short, does not form cerebral infarction, and the pathological and physiological condition of this phase is the cerebral tissue hypoxic-ischemic, but does not cause the structural change of tissue, only is dysfunction in various degree, and CT is last may also to can't see focus.If recover normal blood supply in time, remove some the deleterious metabolite in the ischemic tissue, patient may be recovered fully.This phase is the most desirable opportunity of cerebral infarction treatment, if select thrombolytic therapy, it is generally acknowledged and can receive satisfied curative effect.But experiment finds that with clinical research revascularization, blood reperfusion often make original symptom more serious, and reperfusion injury can take place.Experiment confirm is arranged, vascular occlusion 3～4h (hour) back blood flow full recovery, 3d (day) 2～2.5 times of permanent fully inaccessible increases of back infarct size.Other has many research reports to think, reperfusion injury is almost relevant with all correlative factors: 1. aspect biochemistry, it can cause numerous relevant biochemical substances to change, as neurotransmitter disorder, metabolite too much, thromboxane increases and prostacyclin minimizings, various active neuropeptide disorder, intracellular calcium raise, excitatory amino acid increases and the increasing etc. of the change of inhibitory aminoacid minimizing, cytokine, inflammatory factor.2. aspect molecular biology, it can cause the variation of many related genes, and as ischemic region and occur a large amount of apoptotic cells on every side, antiapoptotic factors obviously raises, the range gene rise that apoptosis is relevant etc.3. aspect morphology, its can make the ischemic tissue of brain cell bad become increase the weight of, edema obviously, infarct size increasing etc.Therefore, when the treatment cerebral infarction, the clinical medicine that more needs is both can be suitable for early stage medication, can effectively prevent reperfusion injury again.
Ischemic cardiomyopathy (ischemic cardiomyopathy, ICM) be meant by coronary atherosclerosis and cause long-term myocardial ischemia, cause myocardium diffuse fibrosis, produce and the continuous increase of the similar clinical syndrome of constitutional dilated cardiomyopathy along with Incidence of CHD, ICM is also day by day serious to the harm that human health caused.At present clinical when the treatment ischemic cardiomyopathy, treatment is exactly to improve myocardial ischemia the most targetedly.As take chemical synthetic drugs such as nitroglycerin, sorbide nitrate, Covera-HS.The problem that these medicines exist is that nitrate esters medicine can produce drug resistance and drug dependence.And the taboo of Covera-HS is more.Chinese medicine is strengthening body resistance and dispelling evil, the principles that dialectical opinion is controlled of adopting when the treatment ischemic cardiomyopathy more.In prescription, be raw material how with the botanical herbs.Its advantage is that drug effect relaxes, and toxic and side effects is little.Weak point is that the raw material resources of many medicines are in short supply, the cost of drugs height.
Ischemic enteropathy generally is meant and because of intestinal wall ischemia, anoxia the disease of infarction takes place finally.Primary disease is more common in trouble arteriosclerosis, the gerontal patient of cardiac insufficiency.Cause the immediate cause of intestinal ischemia mostly to be mesentery artery and vein, particularly superior mesenteric artery because of atherosis or vascular occlusion that thrombosis causes and narrow.Clinical in treatment during ischemic enteropathy, think early diagnosis, early stage thrombolytic, anticoagulant therapy have effect preferably.And in fact, the clinical manifestation of ischemic enteropathy often lacks specificity.Therefore be difficult to usually be made a definite diagnosis in early days.Moreover existing thrombolytic, the anticoagulant that is used for ischemic enteropathy mostly is chemical synthetic drug greatly, and there are many untoward reaction equally in it.Therefore, the clinicist more expects to have the medicine that both can effectively prevent ischemic enteropathy, also can be used for treating ischemic enteropathy to come out.
Summary of the invention
Purpose of the present invention is exactly that a kind of pharmaceutical composition that is used for ischemic diseases will be provided, and the three kind application of this pharmaceutical composition in the pharmaceutical preparation of preparation treatment ischemic diseases are provided simultaneously.
The object of the present invention is achieved like this:
Pharmaceutical composition of the present invention is made up of following materials of weight proportions:
Radix Astragali 5-15 part, Radix Salviae Miltiorrhizae 2-8 part, Rhizoma Chuanxiong 1-5 part, Flos Carthami 1-5 part, Pheretima 1-3 part.
The present invention provides the new medical use of aforementioned pharmaceutical compositions aspect following three simultaneously:
(1) application of aforementioned pharmaceutical compositions in the pharmaceutical preparation of preparation treatment cerebral infarction.
(2) application of aforementioned pharmaceutical compositions in the pharmaceutical preparation of preparation treatment ischemic cardiomyopathy.
(3) application of aforementioned pharmaceutical compositions in the pharmaceutical preparation of preparation treatment ischemic enteropathy.
The present invention has produced good synergism with above-mentioned 5 flavor Chinese herbal medicine, 5 usefulness, and it is in particular in:
(1) pharmaceutical composition of the present invention can effectively improve the cerebral tissue ischemia, reduces the cerebral infarction scope, reduces whole blood viscosity value and plasma fibrinogen, alleviates neurologic defect due to the reperfusion injury, to PC
12Cell has nutrition and promotes the effect of cell proliferation, to H
2O
2The PC that causes
12Apoptosis has protective effect.Therefore the present invention proposes this pharmaceutical composition first and can be applied in the pharmaceutical preparation of preparation treatment cerebral infarction.
(2) but pharmaceutical composition coronary blood flow increasing of the present invention, reduce coronary resistance, reduce degree of myocardial ischemia and scope, improved myocardial ischemia, reduce myocardial infarct size.Therefore the present invention proposes this pharmaceutical composition first and can be applied in the pharmaceutical preparation of preparation treatment ischemic cardiomyopathy.
(3) pharmaceutical composition of the present invention can delay thrombosis in the mesentery blood vessel, has the effect of thrombosis in the dissolving mesentery blood vessel simultaneously, so the present invention proposes this pharmaceutical composition first and can be applied in the pharmaceutical preparation of preparation treatment ischemic enteropathy.
Pharmaceutical composition of the present invention can extract it according to the Chinese herbal medicine extracting technology of routine.Again according to the conventional formulation requirement, the medicinal adjuvant (as excipient, disintegrating agent, adhesive, lubricant, antioxidant, coating materials, coloring agent, aromatic, surfactant etc.) of extract with routine mixed, make oral formulations or ejection preparations such as injection, infusion solution such as granule, capsule, tablet, oral liquid.But the selection of all these dosage forms can not be used to limit protection scope of the present invention.
The present invention provides a kind of drug formulation process at this:
Take by weighing Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, add 3 times of amount 70% soak with ethanol 3 times, each 48 hours, merge ethanol extract, filter, reclaim ethanol to there not being the alcohol flavor, standby.The medicinal residues and the Radix Astragali, Pheretima coarse grain, flos carthami add 8 times of water gagings, decoct 3 times, each 1 hour, collecting decoction filtered, filtrate concentrates, partly merge with alcohol extraction, continue to be concentrated into the clear paste that relative density is 1.25-1.30 (80 ℃), qinghuo reagent adds right amount of auxiliary materials, make clinical acceptable forms, as tablet, oral liquid, capsule, granule etc.
Pharmaceutical composition of the present invention can be used for prevention and ischemic diseasess such as treatment cerebral infarction, ischemic cardiomyopathy and ischemic enteropathy.Also can be used for treating coronary heart disease, arteriosclerosis and mesenteric vein embolism.Its drug effect is with strong points, drug effect is obvious.It is selected for clinical application provides more medication.
When the present invention is used for prevention or disease such as treatment cerebral infarction, ischemic cardiomyopathy or ischemic enteropathy etc., but oral administration or without oral administration.Dosage is also different different because of the weight of dosage form difference and conditions of patients.In clinical practice, should respect doctor's advice.
In general, the adult population takes dose, and every day is more suitable in crude drug amount 22-100g.Intramuscular injection or intravenous injection medication are more suitable in crude drug amount 22-44g every day.
Optimization formula of the present invention is:
10 parts of the Radixs Astragali, 5 parts of Radix Salviae Miltiorrhizaes, 3 parts of Rhizoma Chuanxiongs, 3 parts on Flos Carthami, 1 part of Pheretima.
Pharmaceutical composition of the present invention (hereinafter to be referred as SQNB) has beneficial effect, has obtained confirmation by following test.
Test a SQNB to the focal treatment of cerebral effect of photochemically-induced rat
1, laboratory animal and grouping: male 3 monthly age SD rats, body weight: 200-250g is provided by the PLA General Hospital Experimental Animal Center, animal for cleaning level (quality certification number: D98010), totally 60.Be divided into blank group, SQNB1 group, SQNB2 group and Ginaton medication therapy groups (hereinafter to be referred as the Ginaton group), RONGSHUAN JIAONANG medication therapy groups ((hereinafter to be referred as thrombolytic group), 12 every group at random.
2, experimental technique: behind the 10% chloral hydrate intraperitoneal injection of anesthesia (0.35ml/100g),, separate left top periosteum, expose left top skull in a medisection scalp; Vena femoralis injection 2% rose-red (ROSEBENGA) (SINGMA company produces, molecular weight 1017) 25mg/kg shines left top 10min with cold light source behind the 5min, and cold light source covers surrounding cranial bone apart from skull 5mm with the black step, exposes the about 5 * 8mm of range of exposures
2, 22 ℃ of irradiation temperature.
3, experimental drug and medication:
SQNB (adopting embodiment 1 made medicine); Ginaton tablets: every contains 40mg Folium Ginkgo extract (German Weil-McLain Shu Pei big pharmaceutical factory production, authentication code: X970357, lot number: 2210899); (prestige pharmaceutcal corporation, Ltd far away produces lot number: 20000810) to RONGSHUAN JIAONANG 0.25g/ grain in the Shanxi.
Calculate rat per kilogram of body weight dosage according to adult's dosage and body weight conversion factor than formula.SQNB group rat dosage every day (by the crude drug amount): SQNB1 group 3.2g/kg/ body weight/day, the SQNB2 group is the 6.4g/kg/ body weight/day; Ginaton group 200mg/kg/ body weight/day; Thrombolytic group rat dosage every day is the 213mg/kg/ body weight/day.Each is organized one day dosage of rat and is respectively and is dissolved in the 2ml drinking water and irritates stomach.Administration time is into mould rat postoperative 3h, postoperative 1d, 2d, 3d, 4d, altogether 5d.The blank group gives the equivalent drinking water and irritates stomach.
4, result
4.1 ordinary circumstance is observed
The all appearance activity minimizings in postoperative 2-3d of blank group and treatment group lose weight.Weight increase behind the 3d, fur gloss and brightness gradually take a turn for the better, and the mental status also has clear improvement, and autonomy-oriented is movable to be increased.It is fast slightly than blank group and Ginaton group that SQNB group is recovered, and all do not have significant difference between single.See table 1-1 for details.
Each treatment group different time points body weight change of table 1-1
| Before the art | Postoperative 1d | Postoperative 2d | Postoperative 3d | Postoperative 4d | Postoperative 5d | |
| Matched group | 255.75±14.81 | 244.25±12.41 | 245.7±18.16 | 254.88±19.26 | 261.00±10.89 | 265.63±21.01 |
| The SQNB2 group | 254.13±11.35 | 246.38±13.12 | 259.38±14.25 | 258.14±11.45 | 261.83±15.26 | 266.40±11.38 |
| The SQNB1 group | 256.13±17.26 | 247.88±15.12 | 254.38±16.58 | 257.00±14.32 | 261.38±12.16 | 272.00±15.42 |
| Thrombolytic group | 259.60±11.95 | 245.83±12.15 | 247.00±16.34 | 250.00±15.43 | 253.17±16.17 | 260.16±19.20 |
| The Ginaton group | 256.20±19.21 | 240.60±16.54 | 258.40±14.36 | 266.20±20.02 | 262.20±15.25 | 276.60±14.78 |
4.2 function of nervous system's evaluation
Rat reduces in photochemical induction success back 3h, 1d, 2d autonomic activities, but major part is not seen quadriplegia.The blank group has 2 focus offside fore paw flexing to the inside to occur in postoperative 24h, limitation of activity, and scoring is 1 minute, the Ginaton group has an analogue, and all alleviates in 72h.The performance of SQNB group and thrombolytic group rat impassivity afunction.
4.3 focus of infarct volume
Rat cerebral tissue all sharpness of border, the constant pale focus of infarct of scope occur at the irradiated region cerebral cortex after TTC dyeing.SQNB group and thrombolytic group Infarction volume stove are long-pending all to be reduced than the blank group, and significant difference is (P＜0.001) extremely significantly.Ginaton group infarction stove is long-pending also than blank group little (P＜0.05).SQNB group is compared with the Ginaton group, and the focus of infarct volume is obviously little, statistics there were significant differences property (P＜0.05).See table 1-2 for details
Table 1-2 respectively organizes rat cerebral infarction volume ratio (mean ± standard deviation)
| Group | n | Focus of infarct volume (mm 3) |
| The blank group | 12 | 16.54±5.91 |
| The SQNB2 group | 12 | 5.56±2.41** |
| The SQNB1 group | 12 | 6.09±1.55** ▲ |
| The Ginaton group | 12 | 11.35±4.193* |
| Thrombolytic group | 12 | 7.66±4.44** |
Annotate: * * and blank group be (P＜0.001) relatively; * compare (P＜0.05) with the blank group
▲Compare (P＜0.05) with the Ginaton group
Test two SQNB and line is fastened the therapeutical effect of focal cerebral ischemia of method rat and reperfusion injury
1, laboratory animal and grouping:
Male 3 monthly age SD rats, body weight: 200-250g is provided by the PLA General Hospital Experimental Animal Center, animal for cleaning level (quality certification number: D98010), totally 72.Be divided into sham operated rats, pathology matched group and SQNB group and Ginaton group, thrombolytic group at random, 12 every group.
2, animal model preparation
Rat is with 10% aldehydrol chlorine intraperitoneal injection of anesthesia, flat crouching on operating-table, the extremity cotton rope is fixed, the sterilization visual field, the cervical region median incision, separate left carotid (CCA), external carotid artery (ECA) and internal carotid artery (ICA), respectively at CCA, ICA place threading is carried in order to drawing, and free ECA trunk is pricked with 70 silk threads to lingual artery and jaw aortic bifurcation place and to be tied ECA, it is standby to make a call to a slip-knot at ECA from CCA branch source with 70 silk threads, lift CCA, ICA place threading blocking blood flow is cut off a 0.2mm osculum near ligation place of ECA centrifugal step, 40 silk threads are inserted, ECA near-end slip-knot is pricked dead, loosen CCA, ICA place threading recovers blood flow, cuts off the ECA far-end, and stretching making it is a straight line with ICA, the line bolt is inserted intracranial to anterior cerebral artery, till meeting obstructions through the CCA crotch along ICA.Block the middle cerebral artery opening from the side, the nylon wire insertion depth is by furcation meter 18.5 ± 0.5mm.Sew up skin of neck.Extract the bolt line in postoperative 6h, support the cerebral ischemia-reperfusion injury in rats model.
3, experimental drug and medication are with experiment 1
4, result
4.1 natural death of rat and 7d survival condition:
The natural death number of pathology control rats is up to 50%, and SQNB group natural death ratio drops to 25%, and Ginaton group rats death ratio is 33.33%.The dead ratio of thrombolytic group rat is 41.7%.See table 2-1 for details.
Table 2-1 respectively organizes rats death example number and percentage ratio (%)
| Group | n | Natural death number (%) | The 7d number (%) of surviving |
| Sham operated rats | 12 | 0 (0) | 12 (100) |
| The pathology matched group | 12 | 6 (50) | 6 (50) |
| The SQNB2 group | 12 | 3 (25) | 9 (75) |
| The SQNB1 group | 12 | 3 (25) | 9 (75) |
| The Ginaton group | 12 | 4 (33.3) | 8 (66.7) |
| Thrombolytic group | 12 | 5 (41.7) | 7 (58.3) |
4.2 general situation and body weight change:
Matched group and SQNB organize in postoperative and lassitude all occurs, fur gloss dimness, and the mental status and the fur gloss of postoperative 3dSQNB group rat recover fast than matched group.Weight loss all occurs behind all rat postoperatives, treatment group rat postoperative 3d initial body heavily increases, and the average weight of 7dSQNB group and Ginaton group rat is heavy than the pathology matched group, and statistics has significant difference, and comparing with thrombolytic group also has significant difference.Pathology matched group survival rats weight increase is slower.See table 2-2 for details.
Table 2-2 respectively organizes rat body weight and changes
| Group | Before the art | Postoperative 1d | 2d | 3d | 4d | 5d | 6d | 7d |
| The pathology matched group | 242.1± 8.0 | 232.2± 9.7 | 229.2± 11.8 | 219.1± 10.8 | 223.6± 9.8 | 221.8± 8.8 | 226.7± 7.8 | 235.2± 8.0 |
| The SQNB2 group | 241.2± 8.0 | 227.3± 11.8 | 203.5± 16.8 | 239.2± 14.2 | 243.6± 11.1 | 249.9± 10.8 | 254.2± 13.4 | 260.6± 15.8* ▲ |
| The SQNB1 group | 242.5± 8.0 | 231.5± 10.5 | 227.9± 13.8 | 230.1± 9.8 | 239.3± 13.8 | 242.1± 11.6 | 253.1± 10.8 | 259.9± 11.3* ▲ |
| The Ginaton group | 242.3± 6.8 | 230.1± 12.8 | 232.1± 10.8 | 233.0± 9.8 | 239.5± 9.9 | 240.9± 10.8 | 250.1± 9.0 | 251.9± 8.8* |
| Thrombolytic group | 242.5± 7.2 | 228.5± 20.8 | 210.9± 17.8 | 211.9± 13.8 | 220.3± 12.5 | 230.1± 11.2 | 233.3± 11.1 | 240.1± 11.9 |
Annotate: * and pathology matched group be (P＜0.05) relatively;
▲Compare (P＜0.05) with thrombolytic group
4.3 function of nervous system's appraisal result (seeing table 2-3 for details).
The function of nervous system of postoperative 3h matched group and SQNB group, Ginaton group and thrombolytic group rat marks and does not have significant difference between each component.Postoperative 24 and the scoring of 48h pathology control rats function of nervous system are increased, and dead routine number increases, and the scoring of postoperative 7dSQNB group function of nervous system is low than the pathology matched group, and statistics all has significant difference (P＜0.05).Statistics there was no significant difference (P＞0.05) is compared in all the other each treatment group function of nervous system scorings than the pathology matched group.The scoring of SQNB group function of nervous system is compared with thrombolytic group, and statistics all has significant difference (P＜0.05).See table 2-3 for details.
Show the scoring of 2-3 group rat function of nervous system
| Group | Postoperative | 24h | 2d | 3d | 4d | 5d | 6d | 7d |
| The pathology matched group | 2.1±0.42 | 3.0±0.55 | 3.2±0.53 | 3.2±0.61 | 3.2±0.63 | 2.8±0.60 | 2.6±0.60 | 2.5±0.63 |
| The SQNB2 group | 2.2±0.35 | 2.3±0.63 | 2.3±0.61 | 2.3±0.65 | 2.3±0.59 | 1.8±0.63 | 1.8±0.63 | 1.6±0.60* ▲ |
| The SQNB1 group | 2.5±0.44 | 2.7±0.61 | 2.5±0.62 | 2.5±0.67 | 2.2±0.63 | 1.6±0.61 | 1.6±0.61 | 1.5±0.62* ▲ |
| The Ginaton group | 2.0±0.47 | 2.8±0.63 | 2.6±0.51 | 2.6±0.53 | 2.5±0.60 | 2.4±0.63 | 2.2±0.72 | 2.1±0.73 |
| Thrombolytic group | 2.0±0.35 | 3.0±0.71 | 3.2±0.62 | 3.3±0.61 | 3.2±0.63 | 2.7±0.59 | 2.7±0.59 | 2.6±0.59 |
Annotate: * and pathology matched group be (P＜0.05) relatively;
▲Compare (P＜0.05) with thrombolytic group
4.4 hemorheology and plasma fibrinogen check result:
The whole blood viscosity value of the shear rate (being respectively 200,30,5 and 1) of SQNB group blood and the meansigma methods of plasma fibrinogen are all low than pathology matched group and Ginaton group, and statistics all has significant difference (P＜0.05); But compare statistics with thrombolytic group and do not have significant difference.See table 2-4 for details.
Table 2-4 respectively organizes rat whole blood viscosity (mPas) and plasma fibrinogen check result
| Experimental project | Matched group | The SQNB2 group | The SQNB1 group | The Ginaton group | Thrombolytic group |
| n＝6 | n＝9 | n＝9 | n＝8 | n＝7 | |
| Shear rate 200 | 4.74± 0.27 | 3.05± 0.51* ▲ | 3.19± 0.27* ▲ | 4.39± 0.44 | 3.15± 0.46* ▲ |
| Shear rate 30 | 6.98± 1.65 | 4.33± 1.29* ▲ | 4.64± 1.30* ▲ | 6.24± 2.65 | 4.25± 1.25* ▲ |
| Shear rate 5 | 14.09± 2.16 | 8.21± 2.75** ▲▲ | 8.36± 2.50** ▲▲ | 11.86± 2.39* | 8.28± 3.65** ▲▲ |
| Shear rate 1 | 36.88± 7.72 | 20.43± 6.91** | 20.21± 6.17** ▲▲ | 29.53± 8.93 | 19.53± 7.93** ▲▲ |
| Plasma fibrinogen | 337.9± 21.0 | 210.6± 20.2** ▲▲ | 276.8± 21.1** ▲▲ | 320.7± 27.2 | 200.1± 27.2** ▲▲ |
Compare with the pathology matched group: * P＜0.05 * * P＜0.01; Compare with the Ginaton group:
▲P＜0.05
▲ ▲P＜0.01
4.5 the cerebral infarction stove is long-pending
The mice of survival 7d, anesthesia is put to death, TTC dyeing, the infarction stove amasss graphical analysis.It is long-pending as seen respectively to organize the rat cerebral infarction stove by table 2-5, and SQNB group and Ginaton group infarction stove are long-pending little than the pathology matched group, and all there were significant differences for statistics (P＜0.05).The SQNB group is little than thrombolytic group, and there were significant differences for statistics (P＜0.05), but compare there was no significant difference (P＞0.05) with the Ginaton group.
It is long-pending that table 2-5 respectively organizes the rat cerebral infarction stove
| Group | The cerebral infarction stove amasss (mm 3) |
| Pathology matched group (n=6) | 41.9±7.3 |
| SQNB2 organizes (n=9) | 26.1±6.9* ▲ |
| SQNB1 organizes (n=9) | 26.5±5.2* ▲ |
| Ginaton group (n=8) | 31.3±6.7* ▲ |
| Thrombolytic group (n=7) | 40.7±9.8 |
Compare with the pathology matched group: * P＜0.05; Compare with the RONGSHUAN JIAONANG group:
▲P＜0.05
4.6 cerebral tissue pathology
Dead rat in 48h, the cerebral tissue HE visible pathological changes side cerebral edema that dyes is obvious, and centerline construction is shifted to offside, the tricorn pressurized.Microscopically visible point lamellar hemorrhagic focus in the cerebral infarction focus, neuron number reduce, and are ischemic change, the former because cerebral edema that cerebral ischemia reperfusion injury causes of rats death, cerebral hernia.Other brain general pathology findings of respectively organizing dead rat in the 48h are similar to the pathology matched group.
QNB is to PC for the experiment Three S's
12The nutrition of cell and anti-apoptotic effect
1, laboratory animal and grouping:
Male 3 monthly age SD rats, body weight: 200-250g is provided by the PLA General Hospital Experimental Animal Center, animal for cleaning level (quality certification number: D98010), totally 36.Be divided into matched group, SQNB1 group, SQNB2 group at random, 12 every group.
2, experimental technique:
2.1 contain the SQNB rat blood serum to PC
12The Nutrition of cell
PC
12Cell is by 2 * 10
4Individual/ml is inoculated in 24 orifice plates, adds the EMEM culture medium that contains 10% calf serum, in 37 ℃, and 5%CO
2Overnight incubation (10-12h).Cell is divided into totally 4 groups at random, inhales and to remove original fluid, add respectively and contain 10% and respectively organize in the DMEM culture fluid of rat blood serum and continue to cultivate.Take a picture respectively at 24h, 60h and 86h after the dosing, trypsinization, each group (every group 6 hole) cell of collection are made single cell suspension, and mtt assay is measured OD
595.
2.2SQNB to H
2O
2Due to PC
12Apoptotic protective effect
PC
12Cell is by 2 * 10
4Individual/ml is inoculated in 24 orifice plates, adds the EMEM culture medium that contains 10% calf serum, in 37 ℃, and 5%CO
2Overnight incubation (10-12h).Cell is divided into totally 6 groups at random, inhales and remove original fluid, the normal control group adds and contains 10% calf serum DMEM culture medium; The apoptosis model group adds and contains 100 μ MH
2O
210% calf serum DMEM, SQNB1 group, SQNB1 group add 100 μ MH respectively
2O
2The 10% DMEM culture medium of respectively organizing rat blood serum.Cell is at 37 ℃, 5%CO
2Behind the middle hatching 24h, inhale and remove each hole culture fluid, trypsinization is made single cell suspension with the culture medium that contains 5% corresponding serum, and mtt assay is measured OD
595.
2.3DNA segment fractional analysis
Collect 2 * 10
6Individual cell adds 200 μ l lysate (10mM EDTA, 50mM Tris-HCL, pH8.0,100 μ g/ml E.C. 3.4.21.64s), 56 ℃ of effect 1-2h, equal-volume phenol-chloroform-isoamyl alcohol extracting, centrifugal collection supernatant, 1/10 volume 3M sodium acetate and 2 times of volume ethanol deposit D NA, the centrifugal 15min of 12000 commentaries on classics/min, 70% ethanol is washed precipitation 2 times, air drying, with 10-20 μ l with containing Rnase50 μ g/ml TE dissolving DNA, 1% sepharose electrophoresis, 120V, 12h.
3, experimental drug and medication:
SQNB organizes dose with experiment 1, every rat 2ml, and every morning is irritated stomach once, and matched group gives the equivalent drinking water and irritates stomach, continuous 7d (2ml), 1 time/day.7d afternoon, with 10% aldehydrol chlorine anesthetized rat, abdominal aortic blood rapidly, aseptic separation of serum ,-20 ℃ of preservations.
4, result
4.1MTT method is observed the Nutrition of SQNB to neurocyte
Add different disposal group rat pastille serum effect 24h, 60 and 86h after, SQNB1 group, SQNB2 group rat blood serum are handled cell and are all grown vigorous than matched group, MTT result also shows SQNB group cell number apparently higher than matched group (P＜0.001), and compares no difference of science of statistics between the SQNB group.Show that SQNB can obviously promote cell survival and increment, and do not have dosage and effect relation.See 3-1 for details.
Different time is respectively organized OD after the table 3-1 administration
595Value (x ± SD)
| Group | 24h after the administration | 60h after the administration | 86h after the administration |
| Matched group | 0.27±0.073 | 0.65±0.037 | 1.17±0.074 |
| The SQNB2 group | 0.54±0.036* | 0.91±0.106* | 1.53±0.055* |
| The SQNB1 group | 0.61±0.035* | 1.12±0.125* | 1.52±0.109* |
4.2MTT method is observed the protective effect of SQNB to neuronal apoptosis
Experimental result shows, with 100 μ MH
2O
2Can obviously cause PC
12Apoptosis.The MTT experimental result shows: SQNB presents tangible dose-effect relationship to the protective effect of apoptosis, and heavy dose of (SQNB2 group) produce effects is apparently higher than low dose of (SQNB1 group) (P＜0.001), and the very approaching H that do not add
2O
2The blank group, show that heavy dose of SQNB can almost entirely resist H
2O
2The oxidative damage effect.See 3-2 for details.
Table 3-2SQNB is to H
2O
2Due to PC
12Apoptotic protective effect
| Group | OD 595Value (x ± SD) |
| The blank group | 1.005±0.170** |
| 100μMH 2O 2Group (apoptosis group) | 0.543±0.034 |
| The SQNB2 group | 0.631±0.049 △ |
| The SQNB1 group | 0.795±0.077 △△ |
* compare P＜0.001 with the apoptosis group;
△Compare P＜0.05 with the apoptosis group;
△ △Compare P＜0.001 with the apoptosis group;
4.3DNA segment fractional analysis
100 μ MH
2O
2Obviously DNA ladder appears in cell death inducing.Contain the PC that SQNB group rat blood serum is handled
12Cell, the appearance of DNA ladder obviously alleviates.Experimental result shows that the rat blood serum that contains SQNB has inhibition H
2O
2Induce PC
12Apoptotic effect.
Test the influence of four SQNB to rat clotting time and platelet aggregation rate
1, laboratory animal and grouping:
Male 3 monthly age SD rats, body weight: 200-250g is provided by the PLA General Hospital Experimental Animal Center, animal for cleaning level (quality certification number: D98010), totally 48.Be divided into model group, SQNB1 group, SQNB2 group and Ginaton group at random, 12 every group.
2, experimental technique:
2.1 clotting time detection method
Utilize line to fasten the title cerebral ischemia reperfusion injury model (on seeing) of method, pour into 24h again, 10% water and chloralization.Be fixed on the platform, ventral aorta is taken a blood sample drop of blood on slide, has thread blood coagulation to be as the criterion after provoking with thin Glass rod, the record clotting time.
2.2ADP inductive platelet aggregation rate is measured
10% chloral hydrate intraperitoneal injection of anesthesia is opened the abdominal cavity and is exposed ventral aorta, and from the ventral aorta blood sampling, the ratio of 3.8% sodium citrate and blood is 1: 9, mixing gently after the blood sampling.Every conventional platelet rich plasma (PRP) and platelet poor plasma (PPP) of preparing of rat, the platelet count of utilization biological microscope counting PRP, transferring PRP with PPP is that 45-55 ten thousand/mm3 is (greater than 550,000/mm3 to platelet, adjust with PPP), get each 20 μ l of PRP and PPP and place two cuvettes respectively, add 10 μ l normal saline, mix rearmounted 37 ℃ of insulation 2min, the PRP cup is induced aggreation, response time 5min.Measure maximum assemble (PA) of platelet with platelet aggregation instrument.
3, experimental drug and medication:
Become the mould Mus to give SQNB in postoperative 3h, postoperative 1d, 2d, 3d, 4d, dosage is irritated stomach with experiment one, every rat 2ml, and every morning is irritated stomach once, and model group gives the equivalent drinking water and irritates stomach.
4, result
4.1 cerebral ischemia 3h, pour into 24h again after, the clotting time of SQNB group and Ginaton group rat prolongs than model group, statistics all has significant difference (P＜0.01); And the clotting time of SQNB group rat is compared statistics significant difference (P＜0.05) is arranged with the Ginaton group.See table 4-1. for details
Table 4-1SQNB is to the influence of focal MCAO rat clotting time
| Group | The SQNB1 group | The SQNB2 group | The Ginaton group | Model group |
| Clotting time (s) | 6.58±0.95* △△ | 8.0±0.64* △△ | 5.46±0.93 | 2.57±0.54 |
* compare (P＜0.05) with the Ginaton group
△ △Compare (P＜0.01) with model group
The result shows that the platelet aggregation rate of SQNB group and Ginaton group rat is than model group low (P＜0.01), and the platelet aggregation rate of SQNB group rat is compared with the Ginaton group, and statistics does not have significant difference (P＞0.05).See table 4-2. for details
The influence of platelet aggregation rate when showing 4-2SQNB to focal cerebral ischemia in rats
| Group | The SQNB1 group | The SQNB2 group | The Ginaton group | Model group |
| Platelet aggregation rate | 41.62±4.83** | 38.66±2.44** | 42.04±6.36** | 62.8±5.24 |
* compare (P＜0.01) with model group comparison (P＜0.05) * * and model group
Test five SQNB to the prevention of rat heart muscle ischemic infarct, the effect of treatment
The test example:
Materials and methods
Instrument
16 road physiology monitor (MP-150 types, U.S. BIOPAC), full-automatic blood gas analyzer (ABL5, Denmark), automatic clinical chemistry analyzer (TBA-120FR, Japan), color ultrasound (L4000C1 PR, Korea S), liquid flashing counting device (Wallac, the Pharmacia), full-automatic blood gas analyzer (TBA-120FR, Japan).Reagent and medicine
Creatine kinase (CK), lactic acid dehydrogenase (LDH) test kit are purchased in Beijing Zhongsheng Biological Engineering High Technology Company Endothelin (ET), thromboxance B
2(TxB
2), 6-ketone-prostaglandin F
1α (6-KetoPGF1 α) is put and is exempted from medicine box and purchase the bio-engineering corporation in Beijing Fu Rui, and red tetrazolium is purchased in Tianjin couple stars biotech company.Superoxide dismutase (SOD), malonaldehyde (MDA) test kit are purchased and are built up biological reagent company in Nanjing.
SQNB injection: 10ml/ props up (embodiment 2 is prepared).
RENSHEN JINGYEZAOGAN ZHUSHEYE: Shuangding Pharmaceutical Co., Ltd., Shenyang's preparation.
Laboratory animal
The Wistar rat is purchased in Beijing dimension tonneau China company, and the SPF level is male, body weight 240-260g.The quality certification number: SCX (capital) 2002-0003.
The experiment grouping
1 group of SQNB, 2 groups of SQNB, stem and leaf of Radix Ginseng saponin's group, model group, sham operated rats and normal group.Every group 10.
Duplicating of rat heart muscle ischemia model
The rat coronary ligation improves (with reference to Li Yikui, etc. the herbal pharmacology experimental methodology a little by literature method; Front page, Shanghai science tech publishing house, Shanghai, 1991), under etherization face upward the position and be fixed in operating-table, the 3-4 intercostal is opened breast from the left side, exposes heart, between pulmonary conus and left auricle with No. 0 line ligation arteria coronaria left anterior descending branch immediately, send heart back to thoracic cavity, and extrude thoracic cavity inner blood and gas, and close the thoracic cavity rapidly, open the breast time to be no more than 30S.Sham operated rats is only put suture and not ligation arteria coronaria left anterior descending branch.
Pharmaceutical intervention
Each treated animal in postoperative at once through the sublingual vein administration, normal group and sham operated rats injecting normal saline; 1 group of injection of SQNB SQNB injection 1.8ml/kg; SQNB2 group injection SQNB injection 3.6ml/kg; The stem and leaf of Radix Ginseng saponin organizes injection RENSHEN JINGYEZAOGAN ZHUSHEYE 1.8ml/kg.Each is organized the administration volume and is adjusted to 3.6ml/kg with normal saline.
Index detects
Ultrasound detection
150min after each treated animal administration, 10% chloral hydrate 3ml/kg intraperitoneal injection of anesthesia, the clinostatism of making even cuts off the anterior pectorial region hair, is coated with couplant.The reference literature method (Li Yikui, etc.: the herbal pharmacology experimental methodology; Front page, Shanghai science tech publishing house, Shanghai, 1991) select 9MHz high frequency probe matrix for use, perpendicular to left thoracic wall, and become 10-30 degree angle with breastbone, show the left chamber major axis picture of heart along mitral orifice to apex of the heart direction.To pop one's head in and rotate 90 degree, show left chamber minor axis picture perpendicular to left chamber major axis.Scan depths is adjusted to 4mm, and under the guiding of the ultrasonic left chamber of Type B major axis picture, left ventricular interior diameter maximum (being the papillary muscles level) shows M type ultrasonoscopy, measure left ventricular interior diameter and chamber wall thickness, then sample point is placed the Bicuspid valve place, show doppler ultrasound, measure blood flow rate.Every index is all measured three cardiac cycles, averages, and carries out the left chamber function analysis.Measurement parameter: heart rate (HR), ejection fraction (EF), cardiac output (CO) and left LVSF (FS%).
Left indoor pressure is measured
After each treated animal is finished ultrasound detection, dorsal position is fixed on the operating-table immediately, cut skin and subcutaneous tissue along the throat median line to assigning suprasternal notch at the thyroid cartilage lower edge, separate platysma and deep fascia, dissect to the deep between sternohyoid, sternothyroid and the sternocleidomastoid, expose right carotid, right carotid is separated with vagus nerve, ligation right carotid distal end, the interim folder of bulldog clamp closes the right carotid proximal part, makes diagonal otch on right carotid.Filling heparin-normal saline solution (125U/ml) cardiac catheter in experiment is used is connected with the pressure transducer of 16 road physiology monitor pressure amplifiers, under 16 road physiology monitor prison sides, cardiac catheter drive in the wrong direction is inserted left ventricle along right common carotid artery, wound surface covers with the normal saline gauze behind the A/C, monitor the II lead electrocardiogram simultaneously, stablize animal state 30min, measure left ventricular pressure (LVSP), EDP (LVEDP), again through differential calculation left indoor pressure rising maximum rate (+dp/dt.
Max) and decline maximum rate (dp/dt
Max), and These parameters carried out synchronous recording.
Blood biochemistry index detects
Left indoor pressure is measured and is finished, and gets tremulous pulse, venous blood immediately, and full-automatic blood gas analyzer detects the artery and vein blood oxygen concentration; Extracting arterial blood automatic clinical chemistry analyzer reference reagent box description detects serum creatine kinase (CK), lactic acid dehydrogenase (LDH) is active, superoxide dismutase (SOD) is active, malonaldehyde (MDA) content; Liquid flashing counting device reference reagent box description detects Endothelin (ET), thromboxance B
2(TxB
2), 6-ketone-prostaglandin F
1α (6-KetoPGF1 α).
Myocardial infarct size detects
Get blood and finish, take off heart, normal saline flushing immediately, take by weighing whole-heartedly, left ventricular mass, below the heart ligature, be parallel to coronary sulcus and equably the heart crosscut become 5, place the 1%TTC dyeing liquor then, 37 ℃ were dyeed 5-10 minute, can see that the myocardial ischemia infraction part that is colored presents white, the careful separation white area is weighed, be infarcted region weight, calculate infarcted region and account for left ventricle and dirty whole-heartedly percentage ratio.
Statistical procedures:
Experimental data is represented with x ± s, carries out variance analysis, the F check, and relatively, q checks between group.
Experimental result:
1, SQNB is to the influence (seeing table 5-1, table 5-2 for details) of expeirmental myocardial ischemia rat left chamber function
Table 5-1SQNB is to the influence of expeirmental myocardial ischemia rat heart rate, cardiac output, ejection fraction, left LVSF
Compare * with model group: P＜0.05 * *: P＜0.01
By table 1 as seen, the SQNB group can obviously increase cardiac output, ejection fraction and left LVSF.
The table 5-2SQNB influence intrinsic pressure to expeirmental myocardial ischemia rat left chamber
Compare * with model group: P＜0.05 * *: P＜0.01
By the table 5-2 as seen, SQNB can increase LVSP ,+dp/dt.
Max,-dp/dt
Ma, reduce LVEDP.
This experiment shows: SQNB has coronary blood flow increasing, reduces coronary resistance, reduces the effect of degree of myocardial ischemia and scope, thereby improves myocardial ischemia; The SQNB injection can reduce left chamber EDP simultaneously, blood is easily flowed to the endocardium inferior segment from visceral pericardium, thereby can redistribute coronary artery blood flow;
SQNB is to the influence (seeing Table 5-3) of expeirmental myocardial ischemia rat heart muscle infarction size
Table 5-3SQNB is to the influence of expeirmental myocardial ischemia rat heart muscle infarction size
Compare * with model group: P＜0.05 * *: P＜0.01
By table 5-3 as seen, SQNB can obviously reduce expeirmental myocardial ischemia rat heart muscle infarction size (P＜0.05-0.01).
3SQNB is to the influence (seeing Table 5-4) of expeirmental myocardial ischemia rat heart muscle enzyme
Table 5-4SQNB is to the influence of experimental myocardial infarction rat heart muscle enzyme
Compare * with model group: P＜0.05 * *: P＜0.01
By table 5-4 as seen, SQNB can obviously suppress CK, LDH activity (P＜0.05).
So SQNB has the effect that myocardium enzyme raises, reduces myocardial damage that suppresses.
The SQNB injection is to the influence (seeing Table 5-5) of expeirmental myocardial ischemia rat oxidative damage
Table 5-5SQNB is to the influence of expeirmental myocardial ischemia rat blood serum SOD, MDA
Compare * with model group: P＜0.05 * *: P＜0.01
By table 5 as seen, SQNB can obviously increase expeirmental myocardial ischemia rat blood serum SOD activity, reduces MDA content, compares with model group, and significant difference (P＜0.05-0.01) is arranged.
The influence (seeing Table 5-6) of 5SQNB expeirmental myocardial ischemia rat inner skin cell function
Table 5-6SQNB is to expeirmental myocardial ischemia rat blood serum ET, TxB
2, 6-KetoPGF1 α influence
Compare * with model group: P＜0.05 * *: P＜0.01
By table 6 as seen, SQNB can obviously reduce expeirmental myocardial ischemia rat blood serum ET, TxB
2Concentration, and increase 6-KetoPGF1 α concentration (P＜0.05-0.01).
In sum: SQNB can obviously increase expeirmental myocardial ischemia rat cardiac output, ejection fraction and left LVSF; Increase LVSP ,+dp/dt.
Max,-dp/dt
Ma, reduce LVEDP; Obvious minimizing expeirmental myocardial ischemia rat heart muscle infarction size (P＜0.05-0.01); Obviously suppress CK, LDH activity (P＜0.05); Increase activity of SOD in serum, reduce MDA content; Obviously reduce Serum ET, TxB
2Concentration, and increase 6-KetoPGF1 α concentration (P＜0.05-0.01).Having increases coronary flow, improves myocardial ischemia, reduces the effect of myocardial damage.
Experiment six, SQNB are to thrombotic prevention and thrombolytic effect in the rat mesentery blood vessel
1, laboratory animal and grouping:
Male 3 monthly age Wister rats, body weight: 220-250g is provided by the PLA General Hospital Experimental Animal Center, is divided into matched group, pathology matched group, SQNB group and Ginaton group at random, 12 every group.
2, experimental technique:
Rat is with 20% urethane solution 0.7ml/100g body weight intramuscular anesthesia, by tail vein injection photosensitizer hemoporphyrin 0.125mg/100g body weight, cut off the abdominal part hair, do one in the abdominal part center and be about the 2cm vertical incision, expose small intestinal, rat is placed on is dorsal position on the access panel, pull out small intestinal gently with pincet, and small intestinal launched to be placed on the observation platform, chosen the blood capillary mesentery of winning a prize, selecting diameter is that the normal acellular adherent thin vein of 40-50 μ m blood flow is as the thrombosis target vessel, with 100 watts of mercury lamps of epifluorescence microscope as light source through the UV ultraviolet filter, be radiated on the target vessel spot diameter 200 μ m, illumination 1min observes 10min and record continuously with epifluorescence microscope.
3, experimental drug and medication:
SQNB group and Ginaton group rat 5d before experiment give SQNB (embodiment 1 made medicine) or Ginaton suspension oral gavage (2ml) respectively every day beginning, and 1 time/day, continuous 5d.Dosage is with experiment one.Matched group waits the capacity drinking water to irritate stomach.
4, result
SQNB group rat ultraviolet Continuous irradiation 1min behind the intravenous injection hemoporphyrin, beginning in the blood vessel behind illumination 32sec has platelet adhesion reaction, more late than matched group rat suppository time of occurrence, platelet adhesion reaction also increases gradually after stopping illumination, the part rat suppository forms, but do not stop up tube chamber, blood flow still can pass through, and the part thrombosis is broken up by blood flow.Ginaton group rat 26sec after illumination begins to have the attached wall of platelet, the time that thrombosis occurs is between SQNB and matched group, in the preceding 2min after illumination begins, platelet adhesion reaction is obvious, form the wall bolt, close with the thrombosis size of matched group, when 5-10min, have only the small part mural thrombus to be flushed away.The thrombosis size of SQNB 1min, 10min after illumination all than matched group and Ginaton group little (P＜0.05), the results are shown in Table 6-1, table 6-2..
Table 6-1 respectively organizes rat different time points mesentery vascular peg stay size (μ m
2)
| 1min | 2min | 5min | 10min | |
| The SQNB group | 1600±97* | 1820±112* | 1760±109* | 1690±115* |
| The Ginaton group | 3000±121 | 3020±132 | 2510±88 | 3040±104 |
| Matched group | 3150±107 | 3160±99 | 3410±180 | 3310±134 |
*P＜0.05
The thrombosis area accounts for the percentage ratio (%) of tube chamber in the table 6-2 rat different time points mesentery blood vessel
| 1min | 2min | 5min | 10min | |
| The SQNB group | 39.5 | 41.8* | 32.6* | 40.0* |
| The Ginaton group | 40.1 | 40.7 | 44.5 | 42.4 |
| Matched group | 50.2 | 48.2 | 45.0 | 47.8 |
Embodiment 1
The capsule preparations of medicine of the present invention:
Take by weighing Radix Astragali 5kg, Radix Salviae Miltiorrhizae 2kg, Rhizoma Chuanxiong 1kg, Flos Carthami 1kg, Pheretima 1kg.
The Radix Astragali, Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Flos Carthami, Pheretima are added 8 times of amount 50% ethanol, soak and extract 3 times, each 3 hours, reclaim ethanol, being concentrated into relative density is 1.25 (75 ℃), adds 55% ethanol, carries out precipitate with ethanol, reclaims ethanol, is condensed into clear paste.
Above-mentioned clear paste drying, pulverizing are incapsulated.Every contains crude drug amount 10g.
Embodiment 2
The injection of medicine of the present invention
Take by weighing Radix Astragali 10kg, Radix Salviae Miltiorrhizae 5kg, Rhizoma Chuanxiong 3kg, Flos Carthami 3kg, Pheretima 1kg.
Prepare extract according to embodiment 1 described method.Extract removes the thermal source processing and adds distilled water according to conventional method, regulates isoosmotic pressure with sodium chloride, filters fill.Make the injection that every 10ml contains crude drug amount 20g.
Embodiment 3
The tablet formulation of medicine of the present invention:
Take by weighing Radix Astragali 15kg, Radix Salviae Miltiorrhizae 8kg, Rhizoma Chuanxiong 5kg, Flos Carthami 5kg, Pheretima 3kg.
With Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, add 3 times of amount 70% soak with ethanol 3 times, each 48 hours, merge ethanol extract, filter, reclaim ethanol to there not being the alcohol flavor, standby.The medicinal residues and the Radix Astragali, Pheretima coarse grain, flos carthami add 8 times of water gagings, decoct 3 times, and each 1 hour, collecting decoction filtered, and filtrate concentrates, and partly merges with alcohol extraction, continues to be concentrated into the clear paste that relative density is 1.30 (80 ℃).Made clear paste is added adjuvant, mixed pelletization, be pressed into tablet.Every contains crude drug amount 5g.
Embodiment 4
The oral liquid formulations of medicine of the present invention:
According to embodiment 1 preparation clear paste,, filter fill with made clear paste adding distil water dissolving.Every 100ml contains crude drug amount 40g.
Embodiment 5-7:
The foregoing description is that the consumption proportion of drug component is different, and it can make various dosage forms according to the conventional formulation method, and it all has effect of the present invention.
Claims (2)
1. the application of pharmaceutical composition in the pharmaceutical preparation of preparation treatment ischemic enteropathy of forming by Radix Astragali 5-15 part, Radix Salviae Miltiorrhizae 2-8 part, Rhizoma Chuanxiong 1-5 part, Flos Carthami 1-5 part, Pheretima 1-3 part materials of weight proportions.
2. the application of pharmaceutical composition according to claim 1 in the pharmaceutical preparation of preparation treatment ischemic enteropathy is characterized in that said pharmaceutical composition is made up of following materials of weight proportions: 10 parts of the Radixs Astragali, 5 parts of Radix Salviae Miltiorrhizaes, 3 parts of Rhizoma Chuanxiongs, 3 parts on Flos Carthami, 1 part of Pheretima.
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| CN1262942A (en) * | 1999-01-30 | 2000-08-16 | 赫炎光 | Intravenous injection medicine for curing ischemic cerebrovascular disease and its preparing method |
| CN1541683A (en) * | 2003-11-05 | 2004-11-03 | 济宁华能制药厂 | Antithrombotic Qilong Capsule |
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| CN1262942A (en) * | 1999-01-30 | 2000-08-16 | 赫炎光 | Intravenous injection medicine for curing ischemic cerebrovascular disease and its preparing method |
| CN1541683A (en) * | 2003-11-05 | 2004-11-03 | 济宁华能制药厂 | Antithrombotic Qilong Capsule |
| CN1846737A (en) * | 2005-04-05 | 2006-10-18 | 中国人民解放军兰州军区乌鲁木齐总医院 | Medicine for treating cardiac and cerebral vascular diseases and its prepn process |
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